Diagnostic value of circulating tumor cells in cerebrospinal fluid.

OBJECTIVE: To assess circulating tumor cells in cerebrospinal fluid as a diagnostic approach to identify meningeal metastasis in patients with non-small cell lung cancer by using tumor marker immunostaining-fluorescence in situ hybridization (TM-iFISH). METHODS: In 5 non-small cell lung cancer patients who were confirmed to have developed meningeal metastasis by cerebrospinal fluid cytology, 20 ml of cerebrospinal fluid was obtained through lumbar puncture, from which 7.5 ml was utilized for TM-iFISH to identify and quantitate circulating tumor cells, 10ml for cerebrospinal fluid cytology, and 2.5ml for detection of cerebrospinal fluid tumor markers. RESULTS: TM-iFISH examination identified 18 to 1,823 circulating tumor cells per 7.5ml cerebrospinal fluid. In contrast, cytology assessment revealed tumor cells in only 2 cases. The expression levels of cerebrospinal fluid tumor markers were all increased in all 5 patients when compared with their respective serum levels. Contrast-enhanced MRI scans demonstrated presence of meningeal metastasis in all 5 cases. CONCLUSION: TM-iFISH may become a novel cerebrospinal fluid-based diagnostic strategy to identify circulating tumor cells and meningeal metastasis as compared to traditional diagnostic approaches, although its superior sensitivity and specificity needs to be confirmed through additional studies with a larger sample size.

Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis.

OBJECTIVE: To discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis. METHODS: 5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid. RESULTS: 5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method. CONCLUSION: ARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

A novel methodology to concentrate and quantify malignant cells in CSF from lung cancer patients with leptomeningeal metastasis / 天津医药

Objective To assess the value of tumor marker immunostaining-FISH (TM-iFISH) technology on concen?trating and enumeration of tumor cells in CSF of lung cancer patients with leptomeningeal metastasis(LM). Methods Six cases of non-small cell lung cancer with leptomeningeal metastasis, which were diagnosed by CSF cytology or enhanced MRI scan, were selected. A total of 20 mL of CSF was collected in each case. TM-iFISH technology was employed to concen?trate and quantify circulating tumor cells in 7.5 mL CSF samples in each case while CSF cytology used 10 mL CSF samples in each case;Finally, the rest 2.5 mL CSF in each case was used for biochemistry assay. Results Ten CSF samples from 6 patients with non-small lung cancer with LM were assayed and tumor cells numbers ranging between 3 and 1 823 every 7.5 mL were found in 7 samples. On the other hand, CSF cytology examination only revealed tumor cells in 3 cases. Using CSF biochemical assay, higher than normal of protein level was found in 9 cases. TM-iFISH technology was employed again in 3 cases of patients who received treatment. Tumor cell count in CSF reduced in 2 out of the 3 cases. Conclusion TM-iFISH technology is a new method for detection and enumeration of tumor cells in the CSF in non-small cell lung cancer patients with leptomeningeal metastasis. This technology present diagnosis and curative values in lung cancer patients with leptomen?ingeal metastasis.

ImmunoFISH technology for detection of circulating tumor cells in cerebrospinal fluid to diagnose meningeal metastasis from lung cancer / 中国肿瘤临床

Objective:To investigate the effectiveness of immunoFISH technology in detecting tumor cells in cerebrospinal fluid (CSF) for adjuvant diagnosis of meningeal metastasis from lung cancer. Methods:Circulating tumor cells (CTCs) were detected by im-munoFISH technology in CSF samples from 16 patients with meningeal metastasis from lung cancer and 8 patients with non-tumorous brain diseases. Meningeal metastasis from lung cancer was diagnosed on the basis of neurological symptoms and confirmed by en-hanced magnetic resonance imaging and CSF cytological examination. Results:The number of CTCs was significantly greater in pa-tients with meningeal metastasis from lung cancer than in those with non-tumorous brain diseases (P<0.01). The critical point of the maximum correct diagnosis index (Youden index) was regarded as the judging criterion for the positive tumor cells in CSF based on the receiver operating characteristic curve. When one tumor cell existed in 7.5 mL of CSF, the area under the curve was 0.875, and the 95%confidence interval ranged from 0.705 to 1.000. The diagnostic sensitivity, specificity, effectiveness, positive predictive values, and neg-ative predictive values were 75.0%, 100.0%, 83.3%, 100.0%, and 66.7%, respectively. Conclusion:ImmunoFISH technology provides great significance in detecting CTCs in CSF to diagnose meningeal metastasis from lung cancer.